NSAID use in intervertebral disc degeneration: what are the effects on matrix homeostasis in vivo?

Abstract Background Context: Non-steroidal anti-inflammatory (NSAID) agents are a widely utilized treatment for low back pain (LBP). Literature on NSAID use in articular cartilage has shown detrimental effects; however, minimal data exist to detail the effects of NSAIDs in intervertebral disc degeneration (IDD). As IDD is a major cause of LBP, we explored the effects of indomethacin, a commonly used NSAID, on disc matrix homeostasis in an animal model of IDD. Purpose: To determine the effects of oral indomethacin administration on IDD in an in vivo rabbit model. This study hypothesized that indomethacin use would accelerate the progression of IDD based upon serial imaging and tissue outcomes. Study Design/Setting: This was a laboratory-based, controlled, in vivo evaluation of the effects of oral indomethacin administration on rabbit intervertebral discs. Methods: Six skeletally mature New Zealand White rabbits were divided into two groups: disc puncture alone to induce IDD (Puncture group) and disc puncture plus indomethacin (Punc+Ind group). The Punc+Ind group received daily administration of 6mg/kg oral indomethacin. Serial magnetic resonance imaging (MRI) were obtained at 0, 4, 8, and 12 weeks. MRI index and nucleus pulposus (NP) area were calculated. Discs were harvested at 12 weeks for determination of disc glycosaminoglycan (GAG) content, relative gene expression measured by real time polymerase chain reaction, and histological analyses. Results: MRI index and NP area of punctured discs in the Punc+Ind group demonstrated no worsening of degeneration compared to the Puncture group. Histological analysis was consistent with less severe disc degeneration in the Punc+Ind group. Minimal differences in gene expression of matrix genes were observed between Puncture and Punc+Ind groups. GAG content was higher in animals receiving indomethacin in both annulus fibrosus (AF) and NP at adjacent uninjured discs. Conclusions: Oral indomethacin administration did not result in acceleration of IDD in an in vivo rabbit model. Future research is needed to ascertain long-term effects of indomethacin and other NSAIDs on disc matrix homeostasis.